Adhesion formation is a common complication of cardiovascular surgery, affecting sternal reentry in secondary cardiac surgery and causing other significant complications. The prevention of postsurgical adhesion formation is one of the key elements in addressing this challenge, since adhesions prolong operative time, increase the rates of postoperative complications, and cause heavy bleedings.
In-hospital mortality rate following sternal reentry is 14-15%, whereas for emergency surgery −43%. Fatal hemorrhage occurs in 2-6% of all cases. Various methods with different mechanisms of action, application techniques and efficiency are used to prevent adhesion formation. An ideal method for cardiac surgery is an application of a membrane serving as a temporary barrier, that limits the apposition of sternum and pericardium.
The application of biodegradable membranes composed of natural polymers can effectively prevent the formation of adhesions between opposing wound surfaces during the critical period of healing followed by the membrane's biodegradation to non-toxic products.
The antiadhesion membrane “CV Seprafilm” composed of carboxymethylcellulose and sodium hyaluronate is disclosed by Walter T. et al. (A novel adhesion barrier facilitates reoperations in complex congenital cardiac surgery”/Walther T, Rastan A//The Journal of Thoracic and Cardiovascular Surgery. 2005. Vol. 129, Is. 2.-P. 359-363.)
The employment of such membranes have reduced the rate of postoperative adhesion formation in over 50% of patients. However, the prior art discussed above has met with only limited success as it is less efficient in the presence of blood, particularly in excessive bleedings during open heart surgery or great blood vessel repairs.
Additionally, aggravation of postoperative inflammatory responses induced by “Seprafilm” barriers was reported in the medical literature (Seprafilm-induced peritoneal inflammation: a previously unknown complication/Klingler P J, Floch N R, Seelig M H et al/Report of a case//Dis Colon Rectum-1999.-V. 42.-N. 12.-P. 1639-1643).
Of particular interest are the biodegradable barriers “Repel-CV”, composed of polylactic acid and polyethylene glycol, that are disclosed by Andrew J. L. et al. (Andrew J. L. et al. A Novel bioresorbable film reduces postoperative adhesions after infant cardiac surgery//The Annals Thorac Surg, 2008; V. 86 (2): P. 614-621). These polymers are widely used to fabricate implants and bioresorbable medical devices.
However, the results of the randomized clinical trial assessing the efficiency of “Repel-CV” adhesion barriers reported 21% failure in the studied cohort who had demonstrated severe adhesion formation and a few cases of mediastinitis. Additionally, hydrolysis of polylactic acid polymer chain in vivo is accompanied with the release of lactic acid, provoking significant tissue acidification (pH increases up to 3.2-3.4) and inducing inflammatory tissue response.
Also of interest are antiadhesion membranes composed of polymer belonging to a larger class of materials called polyhydroxyalkanoates (PHAs) that are produced by numerous microorganisms—poly-4-hydroxybutyrate (PHB), dissolved either in 1,4 dioxane, or tetrahydrofuran, that is disclosed in U.S. Pat. No. 7,943,683, IPC C08G63/06, B29C47/00, publ. May 17, 2011. High biocompatibility of polyhydroxyalkanoates is associated with 3-hydroxybutyric acid, that is a normal metabolite of animal and human cells and tissues.
Due to its high biocompatibility, PHB is used as a raw material for the production of absorbable surgical sutures, osteosynthesis devices, surgical plates, and antiahesion membranes. The main disadvantages of the membrane bathers composed of PHB monopolymer are their insufficient elasticity and excessive fragility that may limit the optimal placement of the membrane into the surgical wound, and may cause the failure of the suture—memebrane interface.
In addition, monopolymer dissolution in solvents is accompanied with the release of highly toxic substances, which may form an explosive mixture when it combines with oxygen.
The closest prior invention is a polymeric film composed of 3-hydroxybutyrate and 3-hydroxyvalerate (PHB-3/3-PGV) dissolved in chloroform and loaded with antibiotics or nonsteroidal anti-inflammatory drugs, that is disclosed in RU Pat. No 2447902, A61L31 IPC/08 A61L31/10 A61L31/16.
The employment of polyhydroxybutyrate-hydroxyvalerate copolymer increases the elasticity of the present membranes, compared to those, composed of polyhydroxybutyrate monopolymer. The use of chloroform as a solvent allows minimizing toxic effect.
The main disadvantage in using these antiadhesion membranes is long term biodegradation rate—over three months. The biodegradation rate of membranes for preventing adhesion formation should not exceed 60 days, since adhesions commonly develop between tissue surfaces within 30 days after surgery according to the phases of adhesion genesis. Therefore, long-term employment of antiadhesion bathers in the surgical wound is not recommended as it may provoke the immune response to foreign body.